阿魏酸壳聚糖缓释微球的工艺优化及释药机制研究

 目的 优化离子凝聚法制备阿魏酸壳聚糖微球的工艺，并研究其缓释机制。方法 运用Doehlert设计、多重相应的渴求函数优化法对阿魏酸壳聚糖微球的工艺进行优化。通过显微镜观察和差示热分析研究微球结构和药物状态，探讨释药机制。结果 投药量和交联液pH值对包封率有很大影响。在优化条件下，阿魏酸壳聚糖微球的平均包封率为73.77％，平均载药量为8.08％，药物释放符合Higuchi方程和Weibull分布。药物以微晶状态分布于微球的骨架结构中，未与壳聚糖发生作用。结论 离子凝聚法制备的壳聚糖微球的缓释行为与其网状骨架结构相关。

Technology Optimization of Sustained-Realeasing Chitosan Microspheres Loaded with Ferulic Acid and Their Drug-Releasing Mechanism

OBJECTIVE To prepare 5-aminalsalisylic acid（5-ASA） colon-specific delivery system double coated with pectin-chitosan polyelectrolytecomplex(PEC)-Eudragit films. METHODS The influences of formulations of films on drug release of the delivery system in pH 6.8 PBS were inspected. The abilities of degradation of PEC coated pellets were determined. Relations among swelling capacities, drug release retarding abilities and the degradation abilities of the films were investigated. RESULTS Three colon-specifc charactersitic formulations of the most effective retarding drug release were A. pectin-chitosanⅠ(with molecular weight of 5 lac， degree of deacetylation 72.3%)=3∶1; B. pectin -chitosanⅠ-HPMC=2∶1∶1; C. pectin-chitosanⅡ(with molecular weight of 1 lac， degree of deacetylation 95.4%)=2∶1. The degradation test of films indicated that pellets coated the three formulations with effective retarding drug releasing ability were degradated by colon micro flora. Swelling tests indicated that there were not obvious linearity relation among swelling scales， drug releasing and degradation capacities of the films. The in vitro dissolution simulating transit of the gastrointestinal indicated that double coated pellets effectively retarded drug release. CONCLUSION The 5-ASA pellets double coated by the PEC-Eudrgit have the bimodal drug release， and show favorable colon specific delivery ability.